TY - JOUR
T1 - Requirements for NuMA in maintenance and establishment of mammalian spindle poles
AU - Silk, Alain D.
AU - Holland, Andrew J.
AU - Cleveland, Don W.
PY - 2009/3/9
Y1 - 2009/3/9
N2 - Microtubules of the mitotic spindle in mammalian somatic cells are focused at spindle poles, a process thought to include direct capture by astral microtubules of kinetochores and/or noncentrosomally nucleated microtubule bundles. By construction and analysis of a conditional loss of mitotic function allele of the nuclear mitotic apparatus (NuMA) protein in mice and cultured primary cells, we demonstrate that NuMA is an essential mitotic component with distinct contributions to the establishment and maintenance of focused spindle poles. When mitotic NuMA function is disrupted, centrosomes provide initial focusing activity, but continued centrosome attachment to spindle fi bers under tension is defective, and the maintenance of focused kinetochore fi bers at spindle poles throughout mitosis is prevented. Without centrosomes and NuMA, initial establishment of spindle microtubule focusing completely fails. Thus, NuMA is a defi ning feature of the mammalian spindle pole and functions as an essential tether linking bulk microtubules of the spindle to centrosomes.
AB - Microtubules of the mitotic spindle in mammalian somatic cells are focused at spindle poles, a process thought to include direct capture by astral microtubules of kinetochores and/or noncentrosomally nucleated microtubule bundles. By construction and analysis of a conditional loss of mitotic function allele of the nuclear mitotic apparatus (NuMA) protein in mice and cultured primary cells, we demonstrate that NuMA is an essential mitotic component with distinct contributions to the establishment and maintenance of focused spindle poles. When mitotic NuMA function is disrupted, centrosomes provide initial focusing activity, but continued centrosome attachment to spindle fi bers under tension is defective, and the maintenance of focused kinetochore fi bers at spindle poles throughout mitosis is prevented. Without centrosomes and NuMA, initial establishment of spindle microtubule focusing completely fails. Thus, NuMA is a defi ning feature of the mammalian spindle pole and functions as an essential tether linking bulk microtubules of the spindle to centrosomes.
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U2 - 10.1083/jcb.200810091
DO - 10.1083/jcb.200810091
M3 - Article
C2 - 19255246
AN - SCOPUS:64749087709
SN - 0021-9525
VL - 184
SP - 677
EP - 690
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -